Feasibility and outcomes of robotic sphincter-preserving surgery for rectal cancer after neoadjuvant treatment in patients with preexisting colostomy.

BACKGROUND: Diverting colostomy followed by neoadjuvant treatment is a treatment of choice for obstructive rectal cancer. Such patients may be treated via a robotic approach with several advantages over conventional laparoscopic surgery. Conversely, the existing stoma may interfere with the optimal trocar position and thus affect the quality of robotic surgery. Moreover, the console surgeon does not face the patient, which may endanger the stoma. METHODS: Patients with rectal cancer who underwent sphincter-preserving surgery were retrospectively investigated using a robotic platform after neoadjuvant treatment at our hospital. Based on pretreatment stoma creation, patients were divided into the NS (those without a stoma) and S groups (patients with a stoma). Baseline characteristics, types of neoadjuvant treatment, short-term surgical outcomes, postoperative anorectal manometric data, and survival were compared between the groups. RESULTS: The NS and S groups comprised 65 and 9 patients, respectively. Conversion to laparotomy was required in three patients in the NS group. The S group required a longer console time than the NS group (median: 367 vs. 253 min, respectively, p = 0.038); however, no difference was observed in the total operative time (p = 0.15) and blood loss (p = 0.70). Postoperative complication rates, anorectal function, and oncological outcomes were similar between the groups. CONCLUSIONS: Although console time was longer in patients with a stoma, robotic surgery could be performed safely like in those without a stoma after neoadjuvant treatment.

Incidence of and risk factors for lymphocele formation after lateral pelvic lymph node dissection for rectal cancer: a retrospective study.

AIM: Pelvic lymphocele is a common complication that develops after pelvic lymph node dissection. The incidence of pelvic lymphocele formation has been reported to be 10.5-51% after gynaecological or urological procedures. However, no evidence has been reported thus far with regard to the development of pelvic lymphocele following lateral pelvic lymph node dissection (LPND) for low rectal cancer. The aim of this study was to investigate the incidence of and risk factors for lymphocele formation after LPND for low rectal cancer and to examine its clinical management. METHOD: We retrospectively analysed the incidence of and risk factors for pelvic lymphocele formation after LPND for rectal cancer in our hospital between January 2012 and December 2017. We also compared the size of the lymphocele between asymptomatic and symptomatic patients by using CT volumetry and examined its clinical management. RESULTS: A total of 30 out of 98 patients (30.8%) developed pelvic lymphocele after rectal LPND. The number of resected nodes was significantly higher in patients with a pelvic lymphocele (P < 0.01). The median volume was significantly higher in patients with symptomatic pelvic lymphocele (P = 0.011). Among the nine symptomatic patients, two underwent CT-guided drainage, one underwent transurethral ureteral stent placement and one underwent laparoscopic marsupialization. CONCLUSION: It is essential to keep in mind the possibility of pelvic lymphocele formation during follow-up of patients who undergo LPND, and to consider an appropriate treatment when these patients are symptomatic.

Vascular anatomy of the splenic flexure, focusing on the accessory middle colic artery and vein.

AIM: Recently, the accessory middle colic artery (AMCA) has been recognized as the vessel that supplies blood to the splenic flexure. However, the positional relationship between the AMCA and inferior mesenteric vein (IMV) has not been evaluated. Herein, we aimed to evaluate the anatomy of the AMCA and the splenic flexure vein (SFV). METHOD: Two hundred and five patients with colorectal cancer who underwent enhanced CT preoperatively were enrolled in the present study. The locations of the AMCA and IMV were evaluated, focusing on the positional relationship between the vessels and pancreas - below the pancreas or to the dorsal side of the pancreas. RESULTS: The AMCA was observed in 74 (36.1%) patients whereas the SFV was found in 177 (86.3%) patients. The left colic artery (LCA) was the major artery accompanying the SFV in 87 (42.4%) of patients. The AMCA accompanied the SFV in 65 (32.7%) patients. In 15 (7.8%) patients, no artery accompanied the SFV. The origin of the AMCA was located on the dorsal side of the pancreas in 15 (20.3%) of these 74 patients. Similarly, the destination of the IMV was located on the dorsal side of the pancreas in 65 (31.7%) of patients. CONCLUSION: The SFV was observed in most patients, and the LCA or AMCA was the common accompanying artery. In some patients these vessels were located on the dorsal side of the pancreas and not below it. Preoperative evaluation of this anatomy may be beneficial for lymph node dissection during left-sided hemicolectomy.

Effects of preceding endoscopic treatment on laparoscopic surgery for early rectal cancer.

AIM: Endoscopic treatment for rectal cancer, such as endoscopic mucosal resection and endoscopic submucosal dissection, causes inflammation, oedema and fibrosis in the surrounding tissue. However, little is known about the effect of these endoscopic therapies on salvage laparoscopic rectal surgery. The objective of this retrospective cohort study was to analyse the effect of preceding endoscopic treatment on the outcomes of laparoscopic surgery for rectal cancer. METHOD: We analysed 53 patients who underwent laparoscopic surgery for rectal cancer with clinical Tis or T1 at our department between May 2011 and June 2019. Data from 30 patients who underwent laparoscopic surgery after preceding endoscopic treatment (Group E + S) were compared with those of 23 patients who underwent laparoscopic surgery alone (Group S). RESULTS: There was no significant difference between the groups with respect to preoperative details. The mean operative time tended to be longer in Group E + S, and the volume of intra-operative blood loss was greater in Group E + S than in Group S (median 63 ml vs 10 ml, P = 0.049). There were no significant differences between the groups in other surgical parameters or oncological outcomes. CONCLUSION: Laparoscopic surgery after endoscopic treatment for rectal cancer may be difficult due to an increased risk of intra-operative bleeding. Long-term prognosis after surgery was not affected by preceding endoscopic treatment in rectal cancer.

Utility of computed tomography and 18 F-fluorodeoxyglucose with positron emission tomography/computed tomography for distinguishing appendiceal mucocele caused by mucinous adenocarcinoma from other pathologies.

AIM: Differentiating appendiceal mucocele with mucinous adenocarcinoma from other pathologies before surgery is difficult. The objective of this study was to evaluate the utility of CT and 18 F-fluorodeoxyglucose (FDG) with positron emission tomography (PET)/CT for differentiating mucinous adenocarcinoma of appendiceal mucocele from other pathologies. METHOD: The study included 25 patients who underwent surgery for clinically diagnosed appendiceal mucoceles detected on CT at the University of Tokyo Hospital. Among these patients, 19 underwent FDG-PET/CT preoperatively. We compared features of the CT imaging findings and maximum standard uptake values (SUVmax ) detected by FDG-PET/CT between mucocele with mucinous adenocarcinoma and other pathologies. RESULTS: A total of 13 men (52%) and 12 women (48%) were included in this study, with a median age of 65 years (range 34-83). There were six patients (24%) with pathologically confirmed mucinous adenocarcinoma, 15 patients (60%) with appendiceal mucinous neoplasm and four patients (16%) with simple mucocele caused by chronic inflammation. On the CT findings, wall irregularity was the only significant feature for the two groups in this study (83.3% vs 0.0%, P < 0.01). There was a significant difference in the SUVmax levels on PET/CT between the two groups (100.0% vs 20.0%, P < 0.01). CONCLUSION: Distinguishing between mucocele with mucinous adenocarcinoma and other pathologies using imaging modalities is challenging. Our results suggest that wall irregularity on CT and elevated SUVmax on PET/CT are useful factors that can be employed for such discrimination.

Obstruction is associated with perineural invasion in T3/T4 colon cancer.

AIM: Perineural invasion (PNI) is a risk factor for recurrence and metastasis and consequently leads to decreased survival in patients with various malignancies. Recent studies showed that stent placement in obstructive colon cancer increases the frequency of PNI. We hypothesized that mechanical stress including obstruction itself may be associated with PNI. METHOD: We retrospectively reviewed 496 patients with pathological T3 or T4 colon cancer who did not receive preoperative treatment. Data were collected from medical charts and pathological findings. The relationships between PNI and other clinicopathological factors were analysed using univariate and multivariate analyses. RESULTS: PNI was observed in 239 (48%) patients. Obstruction was markedly more frequent in PNI-positive cancer (39%) than in PNI-negative cancer (24%, P = 0.0003). Multivariate analyses identified obstruction as one of the significant factors associated with PNI (OR 1.68, P = 0.028). Moreover, in 414 patients without distant metastasis who underwent complete resection, PNI was an independent factor associated with poor recurrence-free survival (hazard ratio 2.35, P = 0.003). The coexistence of PNI and obstruction resulted in greater decreases in recurrence-free survival than PNI-negative and/or non-obstructive cases. CONCLUSION: Our results suggest that obstruction is associated with PNI and consequently contributes to an increased postoperative recurrence in colon cancer.

Evaluation of the vascular anatomy of the left-sided colon focused on the accessory middle colic artery: a single-centre study of 734 patients.

AIM: Surgery for colorectal cancer located in the splenic flexure is difficult to perform because of the complex anatomy. Recently, in addition to the middle colic artery and left colic artery (LCA), the accessory middle colic artery (AMCA) has been recognized as a feeding artery for the left-sided colon. This study aimed to evaluate the vascular anatomy of the splenic flexure focusing on the AMCA in a large number of patients. METHOD: A total of 734 patients who underwent CT before surgery for colorectal cancer were enrolled. We retrospectively evaluated the vascular anatomy using both two- and three-dimensional CT angiography. RESULTS: The AMCA existed in 36.4% of the cases (n = 267). In many cases, it originated from the superior mesenteric artery (n = 228, 85.4%). The AMCA had a common trunk with the transverse pancreatic artery in 54 patients (20.2%). The frequency of the presence of the AMCA was associated with the branching pattern of the LCA, and was more frequent when the LCA was absent (P < 0.001). CONCLUSION: The presence of the AMCA is not rare and the AMCA has some branching patterns; therefore, recognizing it preoperatively and intra-operatively is important, being especially careful when the LCA is absent.

The Impact of c-Fos/Activator Protein-1 Inhibition on Allogeneic Pancreatic Islet Transplantation.

Unpreventable allograft rejection is one of the main problems in pancreatic islet transplantation (PIT). Therefore, it is imperative to develop a more effective immunosuppressive strategy. The blockade of transcription factors has been a central part of T cell-depleting immunosuppressive therapies, as typified by the use of calcineurin inhibitors. The inhibition of activator protein-1 (AP-1) offers a novel strategy for immunosuppression in PIT, although to date, no reports on the effects of AP-1 inhibition are available. In this study, we investigated the immunosuppressive effects of T-5224, a c-Fos/AP-1-selective inhibitor, on murine T cells activated by αCD3+αCD28 mAbs. T-5224 inhibited proliferation, CD25 up-regulation, and the production of IL-2 and interferon-γ. In addition, T-5224 blocked the nuclear translocation of c-Fos/AP-1 in activated murine T cells. In BALB/c (H-2(d) )-to-C57BL/6J (H-2(b) ) mouse PIT, the 2-week administration of T-5224 prolonged survival of 600 islet allografts in a dose-dependent manner. When combined with a 2-week low-dose tacrolimus, the T-5224 treatment markedly prolonged allograft survival to over 300 days, while the efficacy was indeterminate when transplanted islet allograft mass was reduced to 300. We conclude that the c-Fos/AP-1 inhibition by T-5224 is a potentially attractive strategy for allogeneic PIT.

Potential Usefulness of Three-dimensional Navigation Tools for the Resection of Intra-abdominal Recurrence of Colorectal Cancer.

PURPOSE: Complete resection of intra-abdominal recurrence of colorectal cancer is difficult because of complex anatomical changes following primary surgery and indefinite cancer demarcation. Here, we demonstrate the effect of surgery using three-dimensional (3D) printed model and 3D virtual images on the achievement of complete resection. METHODS: We enrolled 11 cases who had undergone combined resection of adjacent organs for colorectal cancer recurrence, including localized peritoneal dissemination of colon cancer and local recurrence of rectal cancer, between January 2016 and July 2018. We created 3D virtual images of nine cases and 3D models of two cases and used them for intraoperative navigation. RESULTS: Simulation and navigation using 3D technologies potentially helped the surgeons to comprehend the complex anatomy and perform challenging surgeries. Macroscopic negative margins were achieved in all cases, including R0 resection in 8 of the 11 cases. CONCLUSION: 3D navigation tools are potentially useful to complete the resection of intra-abdominal recurrence of colorectal cancer.

Synergistic effects of 12-O-tetradecanoylphorbol-13-acetate and dexamethasone on de novo synthesis of histidine decarboxylase in mouse mastocytoma P-815 cells.

12-O-Tetradecanoylphorbol-13-acetate (TPA) markedly enhanced the increase in L-histidine decarboxylase (HDC) activity induced by dexamethasone in mouse mastocytoma P-815 cells, even with a concentration of the latter that had the maximal effect, whereas it induced a rapid and transient increase in HDC activity, which peaked after 3 h in the absence of dexamethasone. The synergistic effect of TPA on HDC activity induced by dexamethasone was detected after 4 h, a plateau level being reached by 6 h, which was similar to the time course with dexamethasone alone. TPA enhanced the induction of HDC activity by various glucocorticoids, but had no effect on the induction by dibutyryl cAMP, prostaglandin E2 or sodium butyrate. Both 1-oleoyl-2-acetylglycerol, a protein kinase C activator, and okadaic acid, a protein phosphatase inhibitor, enhanced the increase in HDC activity induced by dexamethasone, but 4 alpha-phorbol-12,13-didecanoate, an inactive derivative of TPA, did not. Protein kinase C inhibitors, such as staurosporin, H-7 and K255a, suppressed the increase in HDC activity induced by TPA with or without dexamethasone. The enhancement of HDC activity by dexamethasone was completely suppressed by cycloheximide or actinomycin D. Furthermore, TPA markedly enhanced the accumulation of HDC mRNA due to dexamethasone (5 to 10-fold, from 6 to 12 h after). TPA did not cause a significant increase in the level of either [3H]dexamethasone binding capacity or preformed HDC activity in cells. These results taken together suggest that dexamethasone-induced de novo synthesis of HDC in mastocytoma P-815 cells is up-regulated by TPA-activated protein kinase C through the mechanism involving an increased rate of transcription.

Synergistic effects of cyclic AMP and Ca2+ ionophore A23187 on de novo synthesis of histidine decarboxylase in mastocytoma P-815 cells.

In the preceding paper (Kawai, H. et al. (1992) Biochim. Biophys. Acta 1133, 172-178), we reported that in mastocytoma P-815 cells dexamethasone and 12-O-tetradecanoylphorbol-13-acetate (TPA) synergistically enhanced the de novo synthesis of L-histidine decarboxylase (HDC). Here we found that Ca2+ acted synergistically with cAMP in the induction of HDC mRNA and HDC activity in mastocytoma P-815 cells, and that the mechanism underlying the enzyme induction by Ca2+ plus cAMP was distinguishable from that by dexamethasone plus TPA. Ca2+ ionophore A23187, itself having no significant activity, markedly enhanced the induction of HDC activity by N6,O2'-dibutyryl cAMP (db cAMP) or cAMP-inducible prostaglandins such as PGE1, PGE2 and PGI2 in the presence of the phosphodiesterase inhibitor, Ro201724. However, A23187 had little effect on increases in HDC activity induced by other known stimulants, such as TPA, dexamethasone and sodium butyrate. These results suggest that A23187 has a specific effect on the induction of HDC activity due to an increased level of cAMP. The finding that both A23187 and cAMP enhanced HDC activity suggests that both Ca2+/calmodulin and cyclic nucleotide dependent protein kinase play essential roles in the process of enhancement of HDC activity. To examine this possibility, we studied the effects of W-7, an inhibitor of calmodulin, removal of extracellular Ca2+, and H-8, an inhibitor of cAMP-dependent protein kinase, on the enhancing activity of A23187 plus db cAMP. The enhancement of HDC activity by A23187 plus db cAMP was inhibited by W-7, removal of extracellular Ca2+, and H-8. The increase in HDC activity was due to the de novo synthesis of the enzyme, since it was suppressed by the addition of cycloheximide or actinomycin D, and was well correlated with the marked accumulation of a 2.7 kilobase HDC mRNA. Furthermore, the mechanism underlying the induction of HDC by db cAMP plus A23187 is distinguishable from that in the case of dexamethasone plus TPA, since preexposure to dexamethasone plus TPA for 12 h, for a plateau level to be reached, did not affect the subsequent increase in HDC activity due to db cAMP plus A23187.

Cell-free and concentrated ascites reinfusion therapy (CART) for management of massive malignant ascites in gastric cancer patients with peritoneal metastasis treated with intravenous and intraperitoneal paclitaxel with oral S-1.

BACKGROUND: Massive malignant ascites originating from peritoneal metastasis of gastric cancer is difficult to control and resistant to chemotherapy. Cell-free and Concentrated Ascites Reinfusion Therapy (CART) is one of the types of apheresis therapy, by which filtered and concentrated ascites containing albumin and globulin is reinfused intravenously to patients. We retrospectively studied the feasibility of intraperitoneal (IP) chemotherapy combined with CART in gastric cancer patients with massive malignant ascites. METHODS: Paclitaxel (PTX) was administered via an IP access port implanted in the subcutaneous space. If patient had massive ascites at the start of treatment, paracentesis was performed through a percutaneous IP catheter and then CART was performed. PTX was administered through the catheter until the ascites diminished. RESULTS: A total of 127 CART procedures in 30 patients were analyzed. The average volume of processed ascites was 3.1 L, which was concentrated to 0.33 L containing 85.5 g protein on average. Significant increases in urine volume, serum total protein and albumin level were found after the CART. Increase in body temperature (0.3°C), decrease in platelet count (3.8 × 10(4)/µl), and changes in blood pressure (2 mm Hg) were found after the CART procedure, but no clinically significant adverse event was experienced. The median survival time and 1-year survival of 30 patients who received IP chemotherapy combined with the CART procedure was 10.2 months and 43.3% respectively. CONCLUSIONS: IP chemotherapy combined with CART might be a promising strategy for patients with massive malignant ascites originating from peritoneal metastasis of gastric cancer.

Does omentectomy prevent malignant small bowel obstruction?

Because the omentum collects and disseminates cancer cells, omentectomy is an integral part of ovarian cancer surgery. We postulate that the omentum serves a similar function in colon cancer and may contribute to post-operative malignant small bowel obstruction (S.B.O.) and that routine omentectomy during colectomy would reduce the incidence of S.B.O. Fischer 344 rats and a transplantable carcinogen-induced rat colon cancer were used to test: (1) whether the omentum is a unique site of intra-abdominal colon tumor implantation which contributes to S.B.O.; and (2) whether omentectomy at the time of tumor implantation would reduce the incidence of S.B.O. Statistical analysis confirmed that animals undergoing omentectomy had a significantly lower incidence of omental tumors and malignant S.B.O. (26 per cent and 16 per cent respectively) when compared with sham operated animals (75 per cent and 85 per cent respectively, P less than 0.001). These data suggest that the omentum is a source of bowel obstruction from implantation and growth of tumour cells in the rat model. Although this could be tested in other animal systems, the addition of routine omentectomy to colectomy is simple, not time-consuming, and may reduce postoperative morbidity.

Do operations facilitate tumor growth? An experimental model in rats.

Enhancement of tumor growth by operation is a concern often expressed by surgeons and patients anticipating cancer surgery. Two series of experiments were performed in which Fischer 344 rats and a carcinogen-induced transplantable rat colon cancer were used to test whether anesthesia and operation facilitate tumor implantation and growth. In the first experiments two groups of rats were given intraperitoneal tumor cells. One group underwent sham laparotomy; the second did not undergo surgery. In the second set of experiments rats were injected subcutaneously with tumor cells and then divided into four groups. The first group did not undergo laparotomy. The second underwent laparotomy on day 1, the third on day 15, and the fourth on days 15 and 29 after tumor implantation. Animals were followed for the incidence and growth rate of tumors that developed. The initial experiments demonstrated that 89% of the operated versus 49% of the nonoperated animals developed a tumor (p less than 0.001). The second experiment demonstrated that: animals undergoing multiple operations have a higher incidence of subcutaneous tumor nodules than nonoperated animals (p less than 0.05); animals undergoing multiple operations have a higher incidence of subcutaneous tumor nodules than animals undergoing a single operation (p less than 0.05); animals undergoing multiple operations had larger size tumor masses than the nonoperated animals (p less than 0.05) and than animals undergoing only one operation (p less than 0.04). This study supports the hypothesis that multiple operations and anesthesia may enhance tumor implantation and growth of metastases. This should be considered when designing therapy for patients with cancer.

Reduction of the allergenicity of soybean by treatment with proteases.

Soybeans were treated with proteases to reduce allergenicity. By immunoblotting with a monoclonal antibody against a major soybean allergen (Gly m Bd 30K), two of eight proteases so far tested were selected to achieve a reduction in allergenicity. Both antigenicity to the monoclonal antibody and allergenicity to the sera from soybean-sensitive patients proved to be markedly reduced by processing with either protease. Thus, soybeans treated with an appropriate protease may possibly be supplied as a hypoallergenic foodstuff for patients.

Febrile seizures: is the EEG a useful predictor of recurrences?

We examined the predictive value of a paroxysmal EEG in children with febrile seizures seen at the University Pediatric Clinic, Skopje, Macedonia, between 1982 and 1984. This was the only facility providing EEG or neurologic consultation for children in Macedonia, and almost all children in the area who experienced a febrile seizure were referred to this facility. EEGs were classified as epileptiform if they contained spikes and sharp waves or spike wave complexes, which were either focal or generalized, and were considered abnormal for age and state. Nonspecifically abnormal was defined as focal or generalized slowing excessive for age and state. Follow-up visits were scheduled at 6-month intervals; mean follow-up time was approximately 23 months. In order to determine whether clearly abnormal EEG features would predict recurrences, we compared the recurrences in 170 children with initial normal-appearing EEGs with 99 children with initial paroxysmal EEGs. There was no significant difference in risk of recurrence of febrile seizures between the two groups; increase in recurrence risk was determined primarily by younger age. The EEG did not add information regarding the likelihood of recurrence of febrile seizures.

[Anesthetic management of a patient with Kimura's disease].

Kimura's disease is a rare disease characterized by granuloma in soft tissues with formation of lymphoid follicles infiltrated with eosinophils. It is accompanied by peripheral eosinophilia and elevated IgE in some patients. Although most patients with Kimura's disease were Japanese, we are not aware of reports about anesthetic management of this disease. We managed a 38-year-old woman with Kimura's disease who underwent a removal of a right preauricular mass with general anesthesia using oxygen, nitrous oxide (50%), and isoflurane (0.5-1.5%). There were no anesthesia-related complications. Anesthetic management of patients with Kimura's disease is also discussed.